We have discovered a change in lamellar mineralization in white female osteoporotics with fracture that separates them from normal controls. The change in mineral pattern is detectable using "biomechanical stereology", a nonlinear, microcracking finite element method we have developed to assess the quality of bone tissue. Bone quality is an area of research independent from investigation of the quantity of bone in the skeleton. The reason for an interest in bone quality is that much of the risk of vertebral fracture is not explained by bone quantity. Data collected since last submission demonstrate first, that biomechanical stereology significantly separates fracture patients from normal subjects, second, that it is an independent predictor of fracture status from stereological measurement of trabecular morphology and also, that the experimentally measured nanoindentation moduli of cancellous bone are predicted by wall thickness (a biological measure of osteoblast function affected by age and osteoporosis) and show a trend for difference between osteoporotic (fracture) patients and controls. The main goals of the proposal are 1) to confirm our result that biomechanical stereology separates fracture patients from normal controls, 2) determine whether bone quality measures can predict the experimental bone strength and toughness of vertebral tissue. The second primary goal (testing for an effect on mechanical properties of vertebral tissue) is essential to determining whether our methods of stratifying bone quality in the ilium are relevant to fracture risk. The hypothesis that bone "quality" differences explains why bone mineral density (BMD) doesn't more accurately predict who will have a fracture is, from the point of view of engineering properties, tantamount to an hypothesis that the microcracking tolerancec, tissue stiffness or some other hard tissue property varies independently of BMD. For the ilium, our preliminary data clearly show that measures of bone quality are different between fracture patients and controls. What is not known is whether these results also apply to vertebral cancellous bone tissue where osteoporotic vertebral fractures actually occur. We have a very large collection of vertebral tissue, spanning the ages of 23-91 years old, with fairly even distribution between male, female, white and black. We will be able to determine whether measures of bone quality add significantly to prediction of tissue strength. [unreadable] [unreadable] [unreadable]